The central role of astrocytes in neurometabolic coupling: A decade's perspective

Abstract

The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function which has provided the basis for 2-deoxyglucose-based functional imaging with PET 1. About ten years ago we provided experimental evidence indicating a central role of astrocytes in neurometabolic coupling 2. The basic mechanism in neurometabolic coupling is the glutamate-stimulated aerobic glycolysis in astrocytes, such that the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and its glycolytic processing, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission 3. Analyses of this coupling have been extended in vivo 4, 5, and recently have also defined the modalities of coupling for inhibitory neurotransmission as well as its spatial extent in relation to the propagation of metabolic signals within the astrocytic syncytium 6, 7. On the basis of a large body of experimental evidence (for a recent review see 8, 9) we have proposed an operational model, 'the astrocyte-neuron lactate shuttle' 10, 11, which has stimulated discussions in the field 12, 13. Recently a series of results obtained by independent laboratories has provided further support for this model 14, 15 – 16. This body of evidence provides a molecular and cellular basis for interpreting data obtained with functional brain imaging studies.